PMID- 21236286
OWN - NLM
STAT- MEDLINE
DCOM- 20110418
LR  - 20151119
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 251
IP  - 2
DP  - 2011 Mar 1
TI  - Mechanism of cytotoxic action of perfluorinated acids. III. Disturbance in Ca(2)+ 
      homeostasis.
PG  - 163-8
LID - 10.1016/j.taap.2011.01.002 [doi]
AB  - The global distribution of perfluorinated acids (PFAs) in industry and in 
      household is well known. Their increasing environmental occurrence and 
      biomagnification in the living organisms have drawn growing interests in efforts 
      to describe precisely the mechanisms of action in vitro and in vivo. Our previous 
      investigations widely described lipophilicity-dependent cytotoxicity of PFAs as 
      well as the effect of perfluorination of carbon chain on depolarization of plasma 
      membrane potential, acidification or mitochondrial dysfunctions. In this study we 
      presented in dose- and time-dependent manner the impact of PFAs on calcium 
      homeostasis in HCT116 cells. Comparative analysis of cytosolic [Ca(2)+](c) and 
      mitochondrial calcium [Ca(2)+](m) carried out by flow cytometry revealed distinct 
      uptake of calcium into mitochondria in correlation to increasing lipophilicity of 
      PFAs. Massive accumulation of [Ca(2)+](m) was not accompanied by equivalent loss of 
      [Ca(2)+](c). Indeed, moderate changes of [Ca(2)+](c) were observed after incubation 
      with 400 muM PFDoDA reaching 29.83% and 49.17% decrease at 4th and 72nd hour, 
      respectively. At the same time, mitochondrial calcium uptake increased from 2- to 
      more than 4-fold comparing with non-treated cells. Incubation with 
      non-fluorinated decanoic acid (DA) did not cause any changes in calcium 
      homeostasis. Presented data show that PFAs-induced perturbations in calcium 
      distribution seem to be a missing link related to mitochondria dysfunction 
      playing a crucial role in determination of apoptotic cell death. Complete scheme 
      for the mechanism of cytotoxic action of PFAs has been included.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Kleszczynski, Konrad
AU  - Kleszczynski K
AD  - Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology, 
      Medical University of Gdansk, ul. Debinki 1, 80-211 Gdansk, Poland.
FAU - Skladanowski, Andrzej C
AU  - Skladanowski AC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110112
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Caprylates)
RN  - 0 (Cytotoxins)
RN  - 0 (Fluorocarbons)
RN  - 947VD76D3L (perfluorooctanoic acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*physiology
MH  - Caprylates/*toxicity
MH  - Cell Membrane/drug effects/metabolism
MH  - Cytotoxins/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Fluorocarbons/*toxicity
MH  - HCT116 Cells
MH  - Homeostasis/*drug effects/physiology
MH  - Humans
EDAT- 2011/01/18 06:00
MHDA- 2011/04/19 06:00
CRDT- 2011/01/18 06:00
PHST- 2010/11/10 00:00 [received]
PHST- 2010/12/20 00:00 [revised]
PHST- 2011/01/04 00:00 [accepted]
PHST- 2011/01/18 06:00 [entrez]
PHST- 2011/01/18 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
AID - S0041-008X(11)00004-4 [pii]
AID - 10.1016/j.taap.2011.01.002 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2011 Mar 1;251(2):163-8. doi: 10.1016/j.taap.2011.01.002. 
      Epub 2011 Jan 12.